Unit of Virus Host-Cell Interactions, UJF-EMBL-CNRS (UMI 3265), 6, rue Jules-Horowitz, 38042 Grenoble Cedex 9, France, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany
Translation initiation in eukaryotes is a precisely regulated process. This event orchestrated by numerous cellular proteins leads to the assembly of the ribosome on the initiation codon located at the 5′ end of mRNA. Under stress conditions, the cellular machinery is impaired resulting in an abrupt drop in the synthesis of the majority of proteins. However, some mRNAs escape this inhibition, which suggests the presence of a pathway different from the traditional cap-dependent process. Several studies have revealed the existence of regulating elements located at the 5′ end of some mRNA. These sequences are called IRES (internal ribosome entry site), and present highly structured regions, folded into independent domains. These IRES allow the translation of some viral and cellular mRNA under conditions where cap-dependent translation is compromised. They thus offer the cell a last resort to translate key genes under difficult cellular conditions. Viral IRESs use this independent pathway to divert the cellular machinery to their own advantage.